Bilkent University, Ankara, Turkey.
Biomacromolecules. 2012 Oct 8;13(10):3377-87. doi: 10.1021/bm301141h. Epub 2012 Sep 28.
Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired self-assembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by self-assembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force-distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies.
淀粉样肽是许多退行性疾病以及维持细胞代谢的重要组成部分。它们独特的稳定结构为开发新材料提供了新的见解。设计受生物启发的自组装肽对于产生新形式的分级纳米结构至关重要。在这里，我们提出了带相反电荷的淀粉样肽（AIP），它们在水中混合时会由于非共价相互作用迅速自组装成纳米纤维，在 pH 为 7 时。用振荡流变学分析自组装 AIP 纳米纤维形成的凝胶的机械性能。自组装 AIP 凝胶表现出的机械性能优于以前报道的合成短肽自组装形成的凝胶。通过 pH 变化中和净电荷来研究由带相反电荷的混合 AIP 分子（AIP-1 + 2）组成的凝胶的流变学研究表明，与通过中和净电荷形成的单个肽网络（AIP-1 和 AIP-2）相比，具有更好的机械稳定性。使用原子力显微镜（AFM）的高分辨率力-距离映射分析了 AIP 混合纳米纤维和电荷中和的 AIP-1、AIP-2 纳米纤维的粘附和弹性特性。自组装的 AIP-1 + 2、AIP-1 和 AIP-2 纳米纤维的纳米力学特性也证实了宏观流变学结果，与分别在酸性和碱性 pH 下自组装的单个 AIP-1 和 AIP-2 纳米纤维相比，AIP 混合纳米纤维的机械稳定性更高。实验结果得到了分子动力学模拟的支持，考虑了氨基酸残基之间的潜在非共价相互作用和可能的聚集形式。此外，在 pH 为 7 时将 HUVEC 细胞培养在 AIP 混合纳米纤维上，观察到纳米纤维系统的生物相容性和胶原蛋白模拟支架特性。在生理条件下，将两性离子染料（罗丹明 B）封装在 AIP 纳米纤维网络中，证明该网络可用于包含可溶性因子作为细胞培养研究的支架。
